crossing96/oncoscreening huggingface dataset:
Long-term risk of progression of carcinoma in situ of the bladder and impact of bacille Calmette-Guérin immunotherapy on the outcome.	OBJECTIVE: This study aimed to determine the long-term risk of cancer progression of carcinoma in situ (CIS) of the urinary bladder, and whether intravesical bacille Calmette-Guérin (BCG) immunotherapy can reduce the risk of progression of CIS. MATERIAL AND METHODS: From a prospectively enrolled cohort of bladder cancer patients treated at Århus University Hospital Skejby, Denmark, between 1994 and 2008, all 163 cases with CIS in the bladder, and a history free of invasive bladder cancer (stage T1-4) at least 1 year prior to inclusion were included in the study. RESULTS: Median follow-up was 51 (0-253) months for progression. Initial treatment consisted of transurethral resection (TUR) alone (109 patients) or TUR plus BCG (54 patients). Twenty-eight patients underwent delayed treatment with BCG. Twenty-one patients in the TUR-alone group (19%) and 42 BCG-treated patients (51%) were free of disease at the end of follow-up (p < 0.001). Progression occurred in 18 BCG-treated patients (22%) versus 31 patients (41%) treated by TUR alone. The 10-year progression-free survival was 62% overall, 50% without BCG and 71% after BCG treatment (p = 0.04). BCG reduced the risk of progression by 46% (hazard ratio 0.54, 95% confidence interval 0.3-0.97). Thirteen patients (9%) experienced progression in the prostate and nine (6%) showed extravesical progression (upper urinary tract or metastases). This was independent of BCG treatment. CONCLUSION: CIS in the absence of invasive (T1) disease carried a 10-year risk of progression of 29?48%. Although BCG was effective against CIS, this effect was limited to the bladder. BCG provided a marginal, but significant reduction in the overall long-term risk of progression.	bladder
Description of a novel murine model for ileocystoplasty and early histologic changes.	There is concern that bladder augmentation with bowel segments predisposes toward the development of carcinoma. Additionally, patients with neurogenic bladder and bladder cancer often present with advanced stage and have poor survival. Cellular hyperproliferation at the urointestinal junction (UIJ) has been implicated in this scenario. We aimed to develop a reproducible murine model of ileocystoplasty (ICP). We also performed preliminary analysis of any early histologic changes with focus on cellular proliferation at the UIJ. Fifteen 6- to 8-week-old female C57BL/6 mice underwent ICP, where a 1-cm ileal segment was used for bladder augmentation. Four sham mice underwent cystotomy and closure, and four mice did not undergo surgery. The mice were euthanized at 12 weeks postsurgery, and paraffin sections were stained for hematoxylin and eosin (H&E). Cellular proliferation was investigated using Ki-67. A novel model of ICP in mice was developed and demonstrated to be technically feasible in approximately 60 min under the operating microscope. Twelve-week postsurgical survival rates were 80% (12 of 15). The surviving mice had a similar weight gain as the sham mice. H&E sections showed thickened urothelium (six to 10 cell layers) at the UIJ, but sparse mitotic figures and no dysplastic changes. Ki-67 staining was rare in the urothelium, and showed no differences between the sham and ICP mice in the bladder or at the UIJ. We here demonstrate the first murine model of ICP. Preliminary studies did not show evidence of early hyperproliferation at the UIJ or in the bladder, but further long-term studies as well as studies with transgenic mice are warranted.	bladder
Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers.	PURPOSE: Epigenetic alterations are common and can now be addressed in a parallel fashion. We investigated the methylation in bladder cancer with respect to location in genome, consistency, variation in metachronous tumors, impact on transcripts, chromosomal location, and usefulness as urinary markers. EXPERIMENTAL DESIGN: A microarray assay was utilized to analyze methylation in 56 samples. Independent validation was conducted in 63 samples by a PCR-based method and bisulfite sequencing. The methylation levels in 174 urine specimens were quantified. Transcript levels were analyzed using expression microarrays and pathways were analyzed using dedicated software. RESULTS: Global methylation patterns were established within and outside CpG islands. We validated methylation of the eight tumor markers genes ZNF154 (P < 0.0001), HOXA9 (P < 0.0001), POU4F2 (P < 0.0001), EOMES (P = 0.0005), ACOT11 (P = 0.0001), PCDHGA12 (P = 0.0001), CA3 (P = 0.0002), and PTGDR (P = 0.0110), the candidate marker of disease progression TBX4 (P < 0.04), and other genes with stage-specific methylation. The methylation of metachronous tumors was stable and targeted to certain pathways. The correlation to expression was not stringent. Chromosome 21 showed most differential methylation (P < 0.0001) and specifically hypomethylation of keratins, which together with keratin-like proteins were epigenetically regulated. In DNA from voided urine, we detected differential methylation of ZNF154 (P < 0.0001), POU4F2 (P < 0.0001), HOXA9 (P < 0.0001), and EOMES (P < 0.0001), achieving 84% sensitivity and 96% specificity. CONCLUSIONS: We initiated a detailed mapping of the methylome in metachronous bladder cancer. Novel genes with tumor, chromosome, as well as pathway-specific differential methylation in bladder cancer were identified. The methylated genes were promising cancer markers for early detection of bladder cancer.	bladder
Factors affecting response to bacillus Calmette-Guérin plus interferon for urothelial carcinoma in situ.	PURPOSE: The unpredictable behavior of carcinoma in situ and its high potential for recurrence and progression make identifying patient characteristics predicting a poor prognosis a priority. We assessed which factors affect the response to bacillus Calmette-Guérin plus interferon-α therapy in patients with urothelial carcinoma in situ. MATERIALS AND METHODS: We analyzed data on a subset of 231 patients with carcinoma in situ enrolled in a multicenter, phase II trial of bacillus Calmette-Guérin plus interferon-α therapy for nonmuscle invasive bladder cancer. Analysis included patients who were bacillus Calmette-Guérin naïve and those with previous exposure to failed bacillus Calmette-Guérin therapy. We evaluated factors potentially affecting the bacillus Calmette-Guérin plus interferon-α response, including patient age, gender, tumor stage, multifocality, prior tumor stage, the previous bacillus Calmette-Guérin failure pattern, courses and maintenance, and prior chemotherapy. RESULTS: The complete response rate at 3 and 6 months in naïve vs previously failed bacillus Calmette-Guérin cases was 76% and 70% vs 76% and 66%, respectively. The 24-month disease-free rate was decreased in the 53 patients with a history of 2 or more failed bacillus Calmette-Guérin courses vs that in the 71 with a history of 1 failed course and bacillus Calmette-Guérin naïve patients (23% vs 57% and 60%, respectively). The 22 patients with refractory carcinoma in situ had the worst outcome of a 23% disease-free rate at 24 months while the 59 with relapse within 1 year had an intermediate outcome of 42% vs 59% in the 33 with relapse after 1 year. Patients with a history of papillary disease did better than those without such a history (p=0.019). CONCLUSIONS: Factors associated with a poor response to bacillus Calmette-Guérin plus interferon-α therapy in patients with carcinoma in situ are prior tumor stage, 2 or more prior bacillus Calmette-Guérin failures and a bacillus Calmette-Guérin failure pattern.	bladder
Palpation device for the identification of kidney and bladder cancer: a pilot study.	PURPOSE: To determine the ability of a novel palpation device to differentiate between benign and malignant tissues of the kidney and bladder by measuring tissue elasticity. MATERIALS AND METHODS: A novel palpation device was developed, mainly composed of a micromotor, a linear position sensor, a force transducer, and a hemisphere tip and cylindrical body probe. Motion calibration as well as performance validation was done. The tissue elasticity of both benign and malignant tissues of the kidney and bladder was measured using this device. A single investigator performed the ex-vivo palpation experiment in twelve kidneys and four bladder specimens. Malignant tissues were made available from partial nephrectomy specimens and radical cystectomy specimens. Palpations for benign renal parenchyma tissue were carried out on nephroureterectomy specimens while non-involved areas in the radical cystectomy specimens were used for benign bladder samples. Elastic modulus (Young's modulus) of tissues was estimated using the Hertz-Sneddon equation from the experimental results. These were then compared using a t-test for independent samples. RESULTS: Renal cell carcinoma tissues appear to be softer than normal kidney tissues, whereas tissues from urothelial carcinoma of the bladder appear to be harder than normal bladder tissues. The results from renal cell carcinoma differed significantly from those of normal kidney tissues (p=0.002), as did urothelial carcinoma of the bladder from normal bladder tissues (p=0.003). CONCLUSION: Our novel palpation device can potentially differentiate between malignant and benign kidney and bladder tissues. Further studies are necessary to verify our results and define its true clinical utility.	bladder
Compliance with guidelines for patients with bladder cancer: variation in the delivery of care.	BACKGROUND: Clinical practice guidelines for the management of patients with bladder cancer encompass strategies that minimize morbidity and improve survival. In the current study, the authors sought to characterize practice patterns in patients with high-grade non-muscle-invasive bladder cancer in relation to established guidelines. METHODS: Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data were used to identify subjects diagnosed with high-grade non-muscle-invasive bladder cancer between 1992 and 2002 who survived at least 2 years without undergoing definitive treatment (n = 4545). The authors used mixed-effects modeling to estimate the association and partitioned variation of patient sociodemographic, tumor, and provider characteristics with compliance measures. RESULTS: Of the 4545 subjects analyzed, only 1 received all the recommended measures. Approximately 42% of physicians have not performed at least 1 cystoscopy, 1 cytology, and 1 instillation of immunotherapy for a single patient nested within their practice during the initial 2-year period after diagnosis. After 1997, only use of radiographic imaging (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.03-1.37) and instillation of immunotherapy (OR, 1.67; 95% CI, 1.39-2.01) were found to be significantly increased. Surgeon-attributable variation for individual guideline measures (cystoscopy, 25%; cytology, 59%; radiographic imaging, 10%; intravesical chemotherapy, 45%; and intravesical immunotherapy, 26%) contributes to this low compliance rate. CONCLUSIONS: There is marked underuse of guideline-recommended care in this potentially curable cohort. Unexplained provider-level factors significantly contribute to this low compliance rate. Future studies that identify barriers and modulators of provider-level adoption of guidelines are critical to improving care for patients with bladder cancer.	bladder
Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation.	Allyl isothiocyanate (AITC) occurs in many commonly consumed cruciferous vegetables and exhibits significant anti-cancer activities. Available data suggest that it is particularly promising for bladder cancer prevention and/or treatment. Here, we show that AITC arrests human bladder cancer cells in mitosis and also induces apoptosis. Mitotic arrest by AITC was associated with increased ubiquitination and degradation of α- and β-tubulin. AITC directly binds to multiple cysteine residues of the tubulins. AITC induced mitochondrion-mediated apoptosis, as shown by cytochrome c release from mitochondria to cytoplasm, activation of caspase-9 and caspase-3, and formation of TUNEL-positive cells. Inhibition of caspase-9 blocked AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC depended entirely on mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser-70. Pre-arresting cells in G(1) phase by hydroxyurea abrogated both AITC-induced mitotic arrest and Bcl-2 phosphorylation. Overexpression of a Bcl-2 mutant prevented AITC from inducing apoptosis. We further showed that AITC-induced Bcl-2 phosphorylation was caused by c-Jun N-terminal kinase (JNK), and AITC activates JNK. Taken together, this study has revealed a novel anticancer mechanism of a phytochemical that is commonly present in human diet.	bladder
Flavones inhibit the proliferation of human tumor cancer cell lines by inducing apoptosis.	Dietary flavonoids have been shown to exert specific cytotoxicity toward some cancer cells, but the precise molecular mechanisms are still not completely understood. In this study, cytotoxic effects of flavones (apigenin and luteolin) on two different cancer cell lines, including human chronic myelogenous erythroleukaemia (K562) and bladder carcinoma (RT112), were determined, and the molecular mechanisms responsible for their cytotoxic effects were studied. The results of an MTT assay showed that luteolin and apigenin were able to induce cytotoxicity in K562 and RT112 cells in a dose- and time-dependent manner. The cytotoxic potency of luteolin was higher than that of apigenin. Flow-cytometry and DNA-fragmentation analysis indicated that the cytotoxicity induced by luteolin and apigenin was mainly due to apoptosis, with minor cell-cycle perturbations. This apoptotic response was characterized by an increase of the sub-G1 fraction of treated cells, poly(ADP-ribose) polymerase proteolysis, typical ladder of DNA fragmentation, and Annexin V-positive cells. In conclusion, luteolin and apigenin exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus, flavones could be considered as potential chemotherapeutic agents.	bladder
Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer.	BACKGROUND: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer. METHODS: Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT. RESULTS: The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events. CONCLUSIONS: This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.	bladder
Urinary bladder: normal appearance and mimics of malignancy at CT urography.	The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists' ability to diagnose bladder cancer.	bladder
Mechanism of monoclonal antibody-coupled Staphylococcus superantigen-A induced apoptosis in human bladder cancer cells.	To investigate the mechanism of apoptosis induced by BDI-1 monoclonal antibody (MAb) coupled Staphylococcal superantigen-A (SEA) in human bladder cancer cell line BIU-87. Human PBMC (effector cells) mediated cytotoxic killing of BIU-87 cells (target cells) was studied by culturing the BIU-87 cells in the presence of effector cells plus medium after their activation by treatment with SEA-targeted by MAb, SEA alone or vehicle (control). Proliferation and apoptosis of BIU-87 cells was measured after the treatments. Expression of Bax and Bcl-2 and cytokine concentration in co-culture supernatants were detected by Western blot and ELISA, respectively. Proliferation of MAb-targeted SEA BIU-87 cells decreased significantly (P < 0.05) as compared to control and SEA groups. Flow cytometry revealed apoptosis in SEA alone and more prominently in targeted-SEA treated in BIU-87 cells, which is significantly more than in controI cells (P < 0.05). In addition, Western blot analysis indicated that the ratio of Bax/Bcl-2 significantly increased by targeted SEA treatment, even at low concentration, as compared to cells treated with SEA alone or control cells (P < 0.05). However, there were no significant differences in IL-2, TNF-α and IFN-γ levels in the culture medium between SEA and targeted SEA groups, even though they are several folds higher than in control cells. SEA targeting by MAb significantly increases apoptosis in BIU-87 cells, possibly through the up-regulation of proapoptotic protein Bax and down regulation of antiapoptotic protein, Bcl-2.	bladder
Fatty acid binding proteins (FABPs) in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma.	BACKGROUND: Fatty acid binding proteins (FABP) play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. METHODS: Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. RESULTS: General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. CONCLUSIONS: Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the same cancer. The FABP patterns in the cell lines do not always reflect the real situation in the tumours. These facts have to be considered in functional studies concerning the different FABPs.	bladder
Urothelial bladder cancer with cavitary lung metastases.	Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Longterm survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis.	bladder
Adult urinary bladder tumors with rhabdomyosarcomatous differentiation: clinical, pathological and immunohistochemical studies.	Adult rhabdomyosarcoma (RMS) in the urinary bladder is rare, and is the subject of case reports and small series. It consists of sheets of small round blue cells with high nuclear cytoplasmic ratio, brisk mitosis and apoptosis. In this study, we reported one case of pure rhabdomyosarcoma and two cases of urothelial carcinomas with extensive rhabdomyosarcomatous differentiation. In addition, their immunohistochemical profile was compared to that of small cell carcinoma of the bladder. Our study showed that sufficient sampling was critical for the diagnosis of urothelial carcinoma with extensive rhabdomyosarcomatous differentiation. As adult RMS in the bladder and urothelial carcinoma with rhabdomyosarcomatous differentiation shared morphological features with small cell carcinoma of the bladder, appropriate immunohistochemical stains were necessary in the differential diagnosis. We showed both rhabdomyosarcoma and rhabdomyosarcomatous areas of the urothelial carcinoma were positive for myogenin, negative for cytokeratin and chromogranin stains. In contrast, small cell carcinoma was positive for cytokeratin, and 7 out of 9 cases were also positive for chromogranin. Both rhabdomyosarcoma and small cell carcinoma could be positive for synaptophysin, a potential pitfall to avoid. In addition, all of the tumors with rhabdomyosarcomatous differentiation were negative for FKHR rearrangement.	bladder